Barium-cross-linked alginate-gelatine microcapsule as a potential platform for stem cell production and modular tissue formation (original) (raw)
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Progress in Biomaterials, 2021
Functional tissue regeneration using synthetic biomaterials requires proliferation and heterotypic differentiation of stem/ progenitor cells within a specialized heterogeneous (biophysical-biochemical) microenvironment. The current techniques have limitations to develop synthetic hydrogels, mimicking native extracellular matrix porosity along with heterogeneous microenvironmental cues of matrix mechanics, degradability, microstructure and cell-cell interactions. Here, we have developed a microenvironment modulating system to fabricate in situ porous hydrogel matrix with two or more distinct tailored microenvironmental niches within microbeads and the hydrogel matrix for multicellular tissue regeneration. Electrosprayed pectin-gelatin blended microbeads and crosslinked alginate hydrogel system help to tailor microenvironmental niches of encapsulated cells where two different cells are surrounded by a specific microenvironment. The effect of different microenvironmental parameters associated with the microbead/hydrogel matrix was evaluated using human umbilical-cord mesenchymal stem cells (hUCMSCs). The osteogenic differentiation of hUCMSCs in the hydrogel matrix was evaluated for bone tissue regeneration. This will be the first report on microenvironment modulating microbead-hydrogel system to encapsulate two/more types of cells in a hydrogel, where each cell is surrounded with distinct niches for heterogeneous tissue regeneration.
Materials Science & Engineering C, 2018
To develop osteogenic building blocks for modular bone tissue engineering applications, influence of gelatin as cell adhesive molecule and nano-hydroxyapatite (nHA) as osteoconductive component was examined on algi-nate-based hydrogel properties and microencapsulated osteoblast-like cell behavior by using factorial experimental design technique. nHA and alginate showed a statistically significant impact on swelling reduction, and improvement of stability and mechanical strength of hydrogels, respectively. Gelatin influence, however, was in a reverse manner. nHA played imperative roles in promoting microencapsulated osteoblastic cell proliferation and function due to its bioactivity and mechanical strength improvement of hydrogels to the modulus range of mineralized bone tissue in vivo. The results and their statistical analysis also revealed the importance of interaction effect of gelatin and nHA. Proliferation and osteogenic function of the cells fluctuated with increasing gelatin concentration of microcapsules in the presence of nHA, demonstrating that hydrogel properties should be balanced to provide an efficient 3D osteoconductive microcapsule. Alginate (1%)-gelatin (2.5%)-nHA (0.5%) microcapsule with compressive modulus of 0.19 MPa ± 0.02, swelling ratio of 52% ± 8 (24 h) and degradation rate of 12% ± 4 (96 h) revealed a maximum performance for the cell proliferation and function, indicating a potential microcapsule composition to prepare building blocks for modular bone tissue engineering.
Biomaterials, 2001
Alginate gels have been used in both drug delivery and cell encapsulation applications in the bead form usually produced by dripping alginate solution into a CaCl bath. The major disadvantages to these systems are that the gelation rate is hard to control; the resulting structure is not uniform; and mechanically strong and complex-shaped 3-D structures are di$cult to achieve. In this work controlled gelation rate was achieved with CaCO }GDL and CaSO }CaCO }GDL systems, and homogeneous alginate gels were formulated as sca!olds with de"ned dimensions for tissue engineering applications. Gelation rate increased with increasing total calcium content, increasing proportion of CaSO , increasing temperature and decreasing alginate concentration. Mechanical properties of the alginate gels were controlled by the compositional variables. Slower gelation systems generate more uniform and mechanically stronger gels than faster gelation systems. The compressive modulus and strength increased with alginate concentration, total calcium content, molecular weight and guluronic acid (G) content of the alginate. MC3T3-E1 osteoblastic cells were uniformly incorporated in the alginate gels and cultured in vitro. These results demonstrated how alginate gel and gel/cell systems could be formulated with controlled structure, gelation rate, and mechanical properties for tissue engineering and other biomedical applications.
Cell-interactive Alginate Hydrogels for Bone Tissue Engineering
Journal of Dental Research, 2001
There is significant interest in the development of injectable carriers for cell transplantation to engineer bony tissues. In this study, we hypothesized that adhesion ligands covalently coupled to hydrogel carriers would allow one to control pre-osteoblast cell attachment, proliferation, and differentiation. Modification of alginate with an RGDcontaining peptide promoted osteoblast adhesion and spreading, whereas minimal cell adhesion was observed on unmodified hydrogels. Raising the adhesion ligand density increased osteoblast proliferation, and a minimum ligand density (1.5-15 femtomoles/cm2) was needed to elicit this effect.
Biomaterials, 2007
We describe a method for creating alginate hydrogels with adjustable degradation rates that can be used as scaffolds for stem cells. Alginate hydrogels have been widely tested as three-dimensional constructs for cell culture, cell carriers for implantation, and in tissue regeneration applications; however, alginate hydrogel implants can take months to disappear from implantation sites because mammals do not produce endogenous alginases. By incorporating poly(lactide-co-glycolide) (PLGA) microspheres loaded with alginate lyase into alginate hydrogels, we demonstrate that alginate hydrogels can be enzymatically degraded in a controlled and tunable fashion. We demonstrate that neural progenitor cells (NPCs) can be cultured and expanded in vitro in this degradable alginate hydrogel system. Moreover, we observe a significant increase in the expansion rate of NPCs cultured in degrading alginate hydrogels versus NPCs cultured in standard, i.e. non-degrading, alginate hydrogels. Degradable alginate hydrogels encapsulating stem cells may be widely applied to develop novel therapies for tissue regeneration.
Tissue engineering. Part A, 2014
Three-dimensional matrices that encapsulate and deliver stem cells with defect-tuned formulations are promising for bone tissue engineering. In this study, we designed a novel stem cell delivery system composed of collagen and alginate as the core and shell, respectively. Mesenchymal stem cells (MSCs) were loaded into the collagen solution and then deposited directly into a fibrous structure while simultaneously sheathing with alginate using a newly designed core-shell nozzle. Alginate encapsulation was achieved by the crosslinking within an adjusted calcium-containing solution that effectively preserved the continuous fibrous structure of the inner cell-collagen part. The constructed hydrogel carriers showed a continuous fiber with a diameter of ~700-1000 μm for the core and 200-500 μm for the shell area, which was largely dependent on the alginate concentration (2%-5%) as well as the injection rate (20-80 mL/h). The water uptake capacity of the core-shell carriers was as high as 9...
Development of double-layered alginate-chitosan hydrogels for human stem cell microencapsulation
THE 4TH BIOMEDICAL ENGINEERING’S RECENT PROGRESS IN BIOMATERIALS, DRUGS DEVELOPMENT, HEALTH, AND MEDICAL DEVICES: Proceedings of the International Symposium of Biomedical Engineering (ISBE) 2019
Microencapsulation is a promising technology for stem cell therapy and tissue regeneration. Our previous work proposed the application of microencapsulation technology for improving allogeneic hematopoietic stem cell transplantation. In this current work, we developed a feasible method for encapsulating human umbilical cord blood-derived hematopoietic stem cells. The cells were initially entrapped in ionic cross-linked alginate beads based on a conventional method. It was noticed that alginate beads were easily dissolved in phosphate-buffered saline with Ca 2+ /Mg 2+ , suggesting a poor stability of alginate beads. Therefore, a double-layered microcapsule was developed by coating the alginate gel with glutaraldehyde cross-linked chitosan. Measurement of relative swelling ratio showed that the double-layered gel could expand 1.49-fold in a rich culture medium. A homogenous cell distribution could be visualized in solid core alginate microcapsule by a DNA staining. Altogether, this study presented a feasible method to fabricate a double-layered alginatechitosan microcapsule for human stem cells.
Alginate-based Hydrogels with Improved Adhesive Properties for Cell Encapsulation
International journal of biological macromolecules, 2015
Hydrogel-based biomaterials are ideal scaffolding matrices for microencapsulation, but they need to be modified to resemble the mechanical, structural and chemical properties of the native extracellular matrix. Here, we compare the mechanical properties and the degradation behavior of unmodified and modified alginate hydrogels in which cell adhesive functionality is conferred either by blending or covalently cross-linking with gelatin. Furthermore, we measure the spreading and proliferation of encapsulated osteoblast-like MG-63 cells. Alginate hydrogels covalently crosslinked with gelatin show the highest degree of cell adhesion, spreading, migration, and proliferation, as well as a faster degradation rate, and are therefore a particularly suitable material for microencapsulation.
Journal of Materials Chemistry B, 2014
Microencapsulation of cells by using biodegradable hydrogels offers numerous attractive features for a variety of biomedical applications including tissue engineering. This study highlights the fabrication of microcapsules from an alginate-gelatin crosslinked hydrogel (ADA-GEL) and presents the evaluation of the physico-chemical properties of the new microcapsules which are relevant for designing suitable microcapsules for tissue engineering. Alginate di-aldehyde (ADA) was synthesized by periodate oxidation of alginate which facilitates crosslinking with gelatin through Schiff's base formation between the free amino groups of gelatin and the available aldehyde groups of ADA. Formation of Schiff's base in ADA-GEL and aldehyde groups in ADA was confirmed by FTIR and NMR spectroscopy, respectively. Thermal degradation behavior of films and microcapsules fabricated from alginate, ADA and ADA-GEL was dependent on the hydrogel composition. The gelation time of ADA-GEL was found to decrease with increasing gelatin content. The swelling ratio of ADA-GEL microcapsules of all compositions was significantly decreased, whereas the degradability was found to increase with the increase of gelatin ratio. The surface morphology of the ADA-GEL microcapsules was totally different from that of alginate and ADA microcapsules, observed by SEM. Two different buffer solutions (with and without calcium salt) have an influence on the stability of microcapsules which had a significant effect on the gelatin release profile of ADA-GEL microcapsules in these two buffer solutions.